This invention describes a process for removing a sulfonyl group from the 1-position of a benzimidazole to allow conversion of the 5-isomer into the 6-isomer and also conversion of the 6-isomer into the 5-isomer.
2-Amino-1,5(6)-substituted-benzimidazole compounds inhibit the growth of certain viruses, such as rhinoviruses, polio (types I, II, III), Coxsackie (A9, A21, B5), echo virus (strains 1, 2, 3, 4), and Mengo virus. Although both the 5- and 6-isomers are useful as antiviral agents, the 6-substituted-2-amino-benzimidazole is generally the more active isomer.
Certain sulfonylbenzimidazole compounds are disclosed in U.S. Pat. Nos. 4,118,742 and 4,174,454. The preparation of these reference compounds follows the methods disclosed in U.S. Pat. Nos. 4,018,790 and 4,118,573. Both of these patents reveal the reaction of a benzimidazole compound and a sulfonyl chloride compound in an organic solvent in the presence of a base.
Thiazolinyl and thiazinyl benzimidazole compounds are prepared by the reaction of a 1-unsubstituted-benzimidazole with a haloalkyl isothiocyanate in an organic solvent in the presence of a base, as described in U.S. Pat. Nos. 4,008,243 and 4,150,028. The references also discuss the compounds use as antiviral agents.
In Chemical Reviews, 48, 397-541 (1951), John B. Wright reports the imidazole ring of benzimidazole compounds is cleaved by an acid halide and water, forming a diamine compound.
Charles Price and Robert Reitsema in "Some Sulfonamide Derivatives of 2-Aminobenzimidazole," Journal of Organic Chemistry, 12, 269-274 (1947) describe the formation of 2-aminobenzimidazole-3-nitrobenzenesulfonate by treating 1-(3-nitrophenylsulfonyl)-2-aminobenzimidazole with sodium hydroxide and acetic acid.